Sexual minority (e.g., non-heterosexual) populations experience higher rates of substance use, problematic substance use, mental health disorders, and health related distress and problems. Unique stressors such as discriminatory experiences, expectations of discrimination, internalization of social stigma, and concealment of sexual orientation, collectively termed sexual minority stress, are the primary explanatory model for these health disparities. The overall goal of this proposal is to build on the candidate's demonstrated track record of working with sexual minority populations by developing expertise in bio-behavioral and clinical research to optimize HIV/AIDS prevention in HIV+, substance-using men who have sex with men (MSM). The career development plan includes advanced training in 1) gene expression, 2) clinical research with substance-using MSM, and 3) advanced statistical methods. Aim 1 of the proposed study will examine the direct and indirect pathways (i.e., through stimulant use) whereby sexual minority stress may be associated with gene expression related to functional inflammatory processes among HIV+, methamphetamine-using MSM. Leveraging the infrastructure of an existing randomized controlled trial with HIV-positive, methamphetamine-using MSM (R01-DA033854; Carrico, PI), the cross- sectional associations among sexual minority stress, stimulant use, and the expression of inflammatory genes will be examined. Aim 2 will develop and pilot test a 10 session, individually-delivered, cognitive-behavioral intervention focused on modifying sexual minority stress responses among HIV-positive MSM who engage in episodic and binge patterns of substance use. This intervention development work will culminate in a pilot randomized controlled trial to test whether this novel sexual minority stress intervention (compared to an attention-control condition) can boost and extend the effects of personalized cognitive counseling, a single session intervention that has demonstrated efficacy for reducing substance use among MSM who are not seeking formal substance abuse treatment. Using outcome data from this pilot randomized controlled trial, the potential clinical utility of the sexual minority stress intervention will be examined with respectto reductions in substance use, sexual minority stress, and inflammatory gene expression. Taken together, this research and training plan will lay the foundation for a planned randomized controlled trial to examine the efficacy of this sexual minority stress intervention for targeting he interrelated epidemics of substance use and HIV/AIDS among MSM.